Transport mechanisms at the blood-brain barrier were studied in the rat. Barrier permeability to nonelectrolytes was linearly related to lipid solubility. Large neutral amino acids cross the blood-brain barrier by facilitated diffusion. The affinity of the cerebrovascular transport system for amino acids is 10-100 fold greater than amino acid transport systems in other tissues, and makes the brain susceptible to imbalances in plasma amino acid concentrations. Cerebrovascular transport of large neutral amino acids did not change significantly in the Fischer-344 rat between 3 and 24 months of age. The cerebrovascular permeability to inorganic ions was low, comparable to a cell membrane, and followed the sequence K greater than Mg greater than Na greater than C1 greater than Ca. The low permeability of the cerebrovascular endothelium to Na was maintained with age in the rat, and the cerebrospinal fluid transfer constant for Na fell by only 18%. Calcium influx into the brain was directly proportional to the plasma concentration of ionized calcium. Ca concentrations in brain and CSF were maintained within 13% of control values during chronic changes of up to 50% in plasma Ca concentration. Ca homeostasis is consistent with active, regulated transport of Ca at the blood-brain barrier.